The present study investigates dose-dependent effects of trans-resveratrol on the membrane fluidity using planar lipid bilayer and liposome models. The complex admittance plots obtained for the lipid bilayer show that resveratrol below 60 μM preferentially interacts with the polar headgroups at the membrane-electrolyte interface, leading to enhanced membrane admittance and vice versa at higher concentrations (>60 μM). This was confirmed using solid-state (13)C and (31)P NMR studies and membrane fluidization studies. The localization of resveratrol in the membrane bilayer was found to alter the membrane rigidity, which resulted in a dose-dependent blebbing and lysis of erythrocytes. The protective effect of trans-resveratrol against DPPH also confirms that its localization in the hydrophobic region prevents lipid peroxidation. The cytotoxic effect of resveratrol on a breast cancer cell line also displays a progressive pattern, indicating possible correlation with its membrane rigidifying properties and localization in the lipid bilayer.